Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection

At this stage in the COVID-19 pandemic, most infections are "breakthrough" infections that occur in individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and ad...

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Published in:Science translational medicine Vol. 17; no. 783; p. eadq1086
Main Authors: Chan, Leslie, Pinedo, Kassandra, Stabile, Mikayla A, Hamlin, Rebecca E, Pienkos, Shaun M, Ratnasiri, Kalani, Yang, Samuel, Blomkalns, Andra L, Nadeau, Kari C, Pulendran, Bali, O'Hara, Ruth, Rogers, Angela J, Holmes, Susan P, Blish, Catherine A
Format: Journal Article
Language:English
Published: United States 29.01.2025
Subjects:
Adaptive Immunity
Adult
Breakthrough Infections
COVID-19 - immunology
COVID-19 - prevention & control
COVID-19 Vaccines - immunology
Female
Humans
Immunity, Innate - immunology
Killer Cells, Natural - immunology
Male
Middle Aged
Monocytes - immunology
Proteomics
SARS-CoV-2 - immunology
Transcriptome
Vaccination
ISSN:1946-6242, 1946-6242
Online Access:Get more information
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Summary:At this stage in the COVID-19 pandemic, most infections are "breakthrough" infections that occur in individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity in breakthrough infections. We performed single-cell transcriptomic, proteomic, and functional profiling of primary and breakthrough infections to compare immune responses from unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave. Breakthrough infections were characterized by a less activated transcriptomic profile in monocytes and natural killer cells, with induction of pathways limiting monocyte migratory potential and natural killer cell proliferation. Furthermore, we observed a female-specific increase in transcriptomic and proteomic activation of multiple innate immune cell subsets during breakthrough infections. These insights suggest that prior SARS-CoV-2 vaccination prevents overactivation of innate immune responses during breakthrough infections with discernible sex-specific patterns and underscore the potential of harnessing vaccines in mitigating pathologic immune responses resulting from overactivation.
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ISSN:1946-6242
1946-6242
DOI:10.1126/scitranslmed.adq1086